Human embryonic stem cells have promising potential for therapeutic use. However, as they are derived by disaggregation of potentially viable human embryos their production and use has serious ethical as well as legal complications. A less controversial alternative could be the use of uniparental embryos with duplicate maternal or paternal genomes that are not viable on their own, but can still form pluripotent ES cells. Uniparental cells can contribute to many adult tissues when combined with normal embryos to form chimeras. It is unclear, however, if this is an advantageous consequence of co-development with fertilized cells, or if uniparental cells can cell-autonomously form certain cell types, including stem cells. It is also not known whether embryonic or fetal cells of uniparental origin will repopulate after being grafted directly into adult tissues, a prerequisite for therapeutic applications. [unreadable] [unreadable] As a functional model to test engraftment of uniparental cells, the investigators will perform hematopoietic reconstitution of adult recipients with uniparental fetal liver cells. Preliminary findings indicate that uniparental cells contribute substantially to the fetal livers of chimeras, including primitive hematopoietic cells. The investigators will characterize uniparental cell contribution to fetal liver hematopoietic stem cells using morphological as well as functional characteristics. Contribution of uniparental cells to stem cell enriched populations of fetal liver will be assessed using cell surface markers. Functionality of uniparental cells will be tested by transplantation of uniparental chimeric as well as enriched uniparental fetal liver cells to irradiated adult recipients and analysis of uniparental contribution to the hematopoietic system of reconstituted recipients. Short- and long-term repopulation as well as the contribution to hematopoietic lineages will be observed. The competitive transplantation experiments will furthermore assess the ability of uniparental cells to compete with fertilized cells. This application will be the first test of the functional potential of uniparental cells transplanted into adults, while simultaneously providing novel information about the consequences of genomic imprinting for stem cell function in both fetal development and in the adult. The results will also provide the basis for two future applications being (1) the role on imprinting in hematopoiesis, and (2) the broader use of uniparental cells for therapeutic application. [unreadable] [unreadable]